Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001372343 | SCV001568980 | likely pathogenic | Nephronophthisis 15 | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 7 of the CEP164 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CEP164 are known to be pathogenic (PMID: 22863007, 28125082, 32367404, 34132027, 34499853). This variant is present in population databases (rs370034077, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CEP164-related conditions. ClinVar contains an entry for this variant (Variation ID: 1062608). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Prevention |
RCV004753300 | SCV005365576 | likely pathogenic | CEP164-related disorder | 2024-09-17 | no assertion criteria provided | clinical testing | The CEP164 c.688-2A>C variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant was reported in a carrier analysis of autosomal recessive inherited retinal diseases (Table S3 in Hanany et al. 2020. PubMed ID: 31964843). This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD. Variants that disrupt the consensus splice acceptor site in CEP164 are expected to be pathogenic. This variant is interpreted as likely pathogenic. |